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CPX-MA-1202: A Phase I/Pilot Study of CPX-351 for Children, Adolescents and Young Adults with Recurrent or Refractory Hematologic Malignancies.

What is the purpose of this study?

PURPOSE: The purpose of this study is to test the safety of a study drug
called CPX-351. This drug has been tested in adults but not yet in children and
adolescents. This study tests different doses of the drug to see which dose is
safer in children and adolescents.

Patients who have blood cancer are being asked to take part in this study .
Blood cancers may include leukemia and lymphoma. Patients able to be in this
study have already been treated with standard chemotherapy for their disease
and the disease is still growing or has come back.

CPX-351 is a drug that is not yet approved by the United States Food and Drug
Administration (FDA) and is only used in research studies like this one.
CPX-351 is made up of two chemotherapy drugs that patients may have already
received called cytarabine and daunorubicin that are now packaged together.

Another purpose of this study is to collect blood samples for special
research studies. Researchers want to study how much of the CPX-351 is in the
body over time. These studies are call pharmacokinetic studies or PK studies
for short. PK studies require the collection of several blood samples before
and after participants are given the study drug.

Detailed Description:

Cytarabine in combination with an anthracycline is a frequently used
chemotherapy platform for both newly diagnosed and relapsed/refractory acute
myeloid leukemia (AML) and other hematologic malignancies. Synergistic
antitumor activity has been demonstrated between cytarabine and daunorubicin
that is dependent upon the ratio of the drugs with the best therapeutic effect
observed with a cytarabine to daunorubicin ratio of 5:1 in in vitro and in vivo
models. CPX-351 is a liposomal preparation of cytarabine and daunorubicin that
maintains this therapeutic drug ratio 24 hours post infusion. The altered
biodistribution from encapsulation may result in a greater therapeutic effect
in patients with relapsed hematologic malignancies and demonstrate greater
tolerability than non-liposomal cytarabine and daunorubicin.

This is a single institution phase-I pilot study that aims to assess the
pharmacokinetics, toxicity and tolerability of CPX-351 in pediatric and young
adults with relapsed/refractory hematologic malignancies. Subjects will receive
a single course of CPX-351 administered on Days 1, 3, and 5. The study will
first open to children in a dose exploration phase, and then be available to an
expanded cohort, which will be open to children and young adults once a
tolerable dose has been determined.

Who can participate?

Inclusion Criteria:

•Age

a. 12 months to 21 years at time of enrollment into dose
exploration phase

a. Acute myeloid leukemia - patients with non-therapy
related AML must be in first or greater relapse or have refractory disease to
at least two courses of induction therapy.

b. Acute lymphoid leukemia - patients with ALL must be in
second or greater relapse or have relapsed disease refractory to re-induction
therapy.

c. Aggressive Lymphoma - patients must have relapsed or
refractory disease for which there is no known curative therapy available.
Patients must have measurable disease by CT scan.

Performance status: Karnofsky > or = to 50% or Lansky > or = to 50.

Prior therapy: Patients must have fully recovered from acute toxicities of
prior therapy.

a. Hematopoetic Stem cell transplant (HSCT): Patients who
relapsed after HSCT, are eligible provided they have no evidence of active
graft versus host disease (GVHD) and are at least 2 months post-transplant.

b. Anthracycline exposure: Patients who have not
previously had TBI (total body irradiation) must have a total previous
cumulative anthracycline exposure ≤ 450 mg/m2 daunorubicin equivalents.
Patients who have had prior TBI or radiation to the mediastinum must have a
previous cumulative anthracycline exposure e ≤ 300 mg/m2 daunorubicin
equivalents.

Cytotoxic therapy:

a. AML and Lymphoma: at least 14 days must have elapsed
since the completion of systemic cytotoxic therapy, with the exception of
hydroxyurea.

b. ALL: patients who relapsed while receiving standard
maintenance therapy do not have a waiting period. At least 14 days must have
elapsed since receiving systemic cytarabine or an
anthracycline/anthracenedione.

c. Intrathecal cytotoxic therapy: no waiting period is
required for patients receiving intrathecal cytarabine, methotrexate and/or
hydrocortisone. At least 14 days must have elapsed since receiving liposomal
cytarabine in intrathecal injection.

b. Adequate Renal function - a maximum serum creatinine
is based on age/gender. Subjects that do not meet eligibility criteria based
upon serum creatinine may meet eligibility criteria based upon a 24 hour
creatinine clearance or radioisotope determined GFR >/= 70 mL/min/1.73 m2.

•Pregnant or breast-feeding women. Males and females of reproductive potential
may not participate unless they have agreed to use an effective method of
contraception.

•Concomitant medications

a. Growth factors- growth factors that support platelet
or white cell number or function must not be administered within 7 days prior
to enrollment.

b. Investigational drugs - patients currently receiving
another Investigational drug are not eligible.

c. Anti-cancer agents- patients who are currently
receiving other anti-cancer agents are not eligible with the exception of
intrathecal cytarabine and oral hydroxyurea. Hydroxyurea must be discontinued
24 hours prior to initiation of protocol therapy.

•Infection: Patients who have an uncontrolled infection are not eligible.

•Patients who in the opinion of the investigator may not be able to comply
with the safety monitoring requirements of the study are not eligible.